1. Field of the Invention
The present invention relates to the field of (trans)peritoneal ventilation of a mammal, preferably a human being, for additional oxygen supply to the organism or individual organs in case of preferably life-threatening need. This occurs in particular in case of insufficient supply of the blood and consequently the body with oxygen due to pulmonary failure. In addition, there can also be oxygen deficiency of individual abdominal organs, e. g. in case of circulatory shock (hypovolemic, septic, etc.). Such conditions can be managed by transperitoneal administration of oxygen from a gas introduced into the abdominal cavity (so-called peritoneal or transperitoneal ventilation), wherein according to the present invention additionally a liquid, preferably aqueous, composition comprising an oxygen carrier such as hemoglobin is used. Unexpectedly, such a liquid composition or solution comprising an oxygen carrier can increase the effectiveness of the diffusion of the oxygen administered by (one-time or repeated) filling or continuous rinsing of the abdominal cavity effectively and in a fast and easy way. This allows peritoneal ventilation to be improved and hypoxia in the body to be addressed more effectively.
The present invention insofar also relates to the presence or use of an oxygen carrier, preferably an oxygen carrier selected from hemoglobin, myoglobin, hemocyanin, erythrocruorin, or derivatives thereof, most preferably native porcine hemoglobin, especially having an oxygen half-saturation partial pressure between 1 and 50 mmHg, for the manufacture of a preferably aqueous composition for enhancement of the diffusion of oxygen (gas) introduced into mucous layers of the peritoneal mucosa, in particular in transperitoneal ventilation.
The invention further relates to a process for preparing a diffusion enhancer for improving oxygen supply of a mammal.
2. Description of the Related Art
In pulmonary failure—e. g. ALI (Acute Lung Injury) and ARDS (Acute Respiratory Distress Syndrome)—inter alia oxygen uptake and supply of the blood with fresh oxygen (oxygenation of the blood) are impaired. This leads to oxygen deficiency in the blood (hypoxemia) and subsequently in the body (systemic hypoxia, insufficient oxygenation of the tissues). For prevention of injury and eventually death, the affected subject must be therapeutically supplied with oxygen. In mild cases, it may suffice to increase the oxygen content in the respiratory air; in more severe cases, ventilation with (end-expiratory) overpressure can also be used. As an ultimate measure, the subject's blood can be loaded with oxygen (oxygenated) outside the body in a mechanical device (oxygenator). Technical oxygenators (e. g. extracorporeal membrane oxygenators, ECMOs) are used also during surgery, e. g. on the heart or the lungs (e. g. in the context of a so-called heart-lung machine). Their use is very complex and demanding, as well as very risky.
Moreover, there are medical conditions that are associated with reduced oxygenation of the organs in the abdominal cavity, i. e. local hypoxia, such as hypovolemic or septic circulatory shock, intestinal infarction, etc., as well as such as require temporary therapeutic increase of oxygenation of organs in the abdominal cavity (e. g. implantation of insulin-producing Langerhans cells into the liver, etc.), in which local improvement in oxygenation is medically desirable.
Various attempts have been made to develop new workable methods to overcome systemic or local hypoxia, in particular to avoid risks and obviate the need for elaborate technical devices, which may be unavailable in case of need. Thus, as an alternative method of non-pulmonary respiratory support, therapeutic oxygen supply via the mucous membrane of the abdominal cavity (the peritoneum, a serosa) has been considered.
A principal approach to (trans)peritoneal oxygenation is one-time or repeated filling or continuous rinsing of the abdominal cavity with an oxygen-rich liquid (comprising already dissolved oxygen). Appropriate compositions are or comprise e. g. oxygen-supersaturated aqueous salt solutions, or, preferably, also oxygenated (per)fluorocarbons. U.S. Pat. Nos. 4,657,532 and 4,963,130 as well as EP 0 209 128 B1 describe such a method of filling the abdominal cavity with oxygenated liquid fluorocarbon compounds or emulsion compositions comprising the same.
Another method is the use of oxygen-comprising gas in the form of peritoneal ventilation. This has been described e. g. by Zhang J.-Y., et al. in “Effect of Oxygenation of Transperitoneal Ventilation on the Death Time After Asphyxiation in Rabbits”, Minerva Anesthesiologica 2010; 76: 913-918 by way of an experiment in rabbits, where detectable amounts of oxygen entered the animals' bodies (significantly prolonging their survival times).
In contrast to this, Giffin D. M., et al. report in “Oxygen Uptake during Peritoneal Ventilation in a Porcine Model of Hypoxemia”, Critical Care Medicine 1998; 26: 1564-1568, using an anesthetized pig model, that in these larger organisms no significant increase in oxygen uptake is achieved by peritoneal ventilation.
None of the experimental methods listed has made it to clinical application readiness. Due to the different and sometimes contradictory results, no general method can be derived from these either.